• Maximum tolerated dose as measured by safety and observed data collected every 28 days [ Designated as safety issue: Yes ]
  

• Antitumor activity as measured by CT, MRI, or positron emission test (PET) scans at every other course [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine the maximum tolerated dose of gemcitabine and flavopiridol in patients with solid tumors.

Secondary

• Determine the safety profile and toxic effects of this regimen in these patients.
• Determine the pharmacokinetics of flavopiridol with and without gemcitabine in these patients.
• Determine, using pharmacodynamic assays, the activity of flavopiridol as a cdk inhibitor in these patients.
• Determine, using pharmacodynamic assays, the markers of this regimen in these patients.

OUTLINE: This is a dose-escalation, multicenter study.

Some patients receive an initial dose of flavopiridol IV over 1-7 hours on day 1 (course 0). Beginning 1 week later and for all subsequent courses, all patients receive gemcitabine IV over 60-150 minutes on days 1 and 15 and flavopiridol IV over 1-7 hours on days 2 and 16. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of gemcitabine and flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, up to 10 additional patients receive treatment at that dose.

Patients are followed at 30 days after study completion.

PROJECTED ACCRUAL: A total of 40-80 patients will be accrued for this study.

DISEASE CHARACTERISTICS:

• Histologically confirmed solid tumor for which gemcitabine is a treatment option OR for which no efficacious therapy exists

• Must meet criteria for 1 of the following:

  • Measurable disease

    • At least 1 unidimensionally measurable lesion at least 20 mm by conventional techniques OR at least 10 mm by spiral CT scan

  • Nonmeasurable disease, including any of the following:

    • Small lesions (less than 20 mm by conventional techniques OR less than 10 mm by spiral CT scan)
    • Bone lesions
    • Cytologically positive pleural or peritoneal disease
    • Elevated tumor markers (e.g., carcinoembryonic antigen, CA 125, CA 19-9, or other tumor marker)
    • Multinodular or confluent nonmeasurable pulmonary, hepatic, adrenal, intra-abdominal, or skin metastases

• No active CNS metastases

  • Previously treated CNS metastases must be stable with no symptoms for 4 weeks after completion of treatment AND patient must be off steroid therapy or on a stable dose for at least the past 2 weeks
• No known leptomeningeal metastases

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-1

Life expectancy

• Not specified

Hematopoietic

• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3

Hepatic

• See Disease Characteristics
• Bilirubin no greater than 1.5 mg/dL
• SGOT no greater than 2.5 times upper limit of normal

Renal

• See Disease Characteristics
• Creatinine no greater than 1.5 mg/dL OR
• Creatinine clearance at least 50 mL/min

Cardiovascular

• None of the following within the past 6 months:

  • Myocardial infarction
  • Unstable angina
  • Transient ischemic attack
  • Cerebrovascular accident
• No new cardiac arrhythmia possibly related to cardiac ischemia
• No large and potentially symptomatic pericardial effusion
• No cardiac disease that would preclude study participation

Pulmonary

• See Disease Characteristics
• No pulmonary embolism within the past 6 months
• No large and potentially symptomatic pleural effusion
• No pulmonary disease that would preclude study participation

Gastrointestinal

• No intractable emesis
• No grade 2 or greater chronic diarrheal disease within the past 6 months

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No active infection
• No severe malnutrition

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Not specified

Chemotherapy

• No more than 2 prior chemotherapy regimens

  • Prior combined modality therapy (e.g., full-dose chemotherapy with radiosensitizing chemotherapy and radiotherapy) is considered 1 prior regimen if all therapy was delivered as part of 1 comprehensive treatment plan
• More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
• No other concurrent chemotherapy

Endocrine therapy

• See Disease Characteristics

Radiotherapy

• See Chemotherapy
• At least 6 months since prior radiotherapy to the lung parenchyma or mediastinum and no evidence of radiation pneumonitis on chest CT scan
• At least 4 weeks since other prior radiotherapy and recovered
• No prior radiotherapy to more than 50% of marrow volume
• No concurrent radiotherapy

Surgery

• Not specified